Perioperative hypotension (MAP <70 mm Hg) was found to be a significant predictor of spinal cord ischemia; hence, careful monitoring and prompt correction of arterial pressure may prevent the development of paraplegia. When the latter occurred, reduction of the CSF pressure by drainage was useful. Patients with a previous or synchronous abdominal aortic repair may also benefit from CSF drainage as a perioperative adjunct.
Rationale:
microRNAs (miRNAs) modulate gene expression by repressing translation of targeted genes. Previous work has established a role for miRNAs in regulating vascular smooth muscle cell (VSMC) activity. Whether circular RNAs are involved in the modulation of miRNA activity in VSMCs is unknown.
Objective:
We aimed to identify circular RNAs interacting with miRNAs enriched in VSMCs and modulating the cells’ activity.
Methods and Results:
RNA sequencing and bioinformatics identified several circular RNAs enriched in VSMCs; however, only one, possessing multiple putative binding sites for miR-145, was highly conserved between mouse and man. This circular RNA gemmed from alternative splicing of Lrp6 (lipoprotein receptor 6), a gene highly expressed in vessels and implicated in vascular pathologies and was thus named circ_Lrp6. Its role as a miR-145 sponge was confirmed by determining reciprocal interaction through RNA immunoprecipitation, stimulated emission depletion microscopy, and competitive luciferase assays; functional inhibition of miR-145 was assessed by measuring expression of the target genes ITGβ8 (integrin-β8), FASCIN (fascin actin-bundling protein 1), KLF4 (Kruppel-like factor 4),
Yes1
(YES proto-oncogene 1), and
Lox
(lysyl oxidase). The interaction was preferentially localized to P-bodies, sites of mRNA degradation. Using loss- and gain-of-function approaches, we found that circ_Lrp6 hindered miR-145-mediated regulation of VSMC migration, proliferation, and differentiation. Differential expression of miR-145 and circ_Lrp6 in murine and human vascular diseases suggests that the ratio of circ_Lrp6 bound to miR-145 versus unbound could play a role in vascular pathogenesis. Viral delivery of circ_Lrp6 shRNA prevented intimal hyperplasia in mouse carotids.
Conclusions:
circ_Lrp6 is an intracellular modulator and a natural sponge for miR-145, counterbalancing the functions of the miRNA in VSMCs.
Background Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence.Methods ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362.
Total debranching of the arch for "zone 0" aneurysms allowed to obtain a longer proximal aortic landing zone with lower incidence of endoleak, however a higher risk of cerebrovascular accident was observed. The relatively high incidence of adverse events in "zone 1" could be associated to a shorter proximal neck, therefore this landing zone is reserved for patients unfit for sternotomy. In case of endoleak, discovered after a satisfactorily positioned endograft in the arch, the rate of spontaneous resolution within the first 6 months is high.
These data provide insight into potential therapeutic benefit of the PETTICOAT technique. A significant immediate increase in TL could be achieved with resolution of all cases of dynamic malperfusion and TL collapse. A different behavior of volumes in the thoracic and abdominal segments was observed.
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